title: Lipid pathway alterations in Parkinson's disease primary visual cortex.
abstract: BACKGROUND
  We present a lipidomics analysis of human Parkinson's disease tissues. We have focused on the primary visual cortex, a region that is devoid of pathological changes and Lewy bodies; and two additional regions, the amygdala and anterior cingulate cortex which contain Lewy bodies at different disease stages but do not have as severe degeneration as the substantia nigra.
  
  
  RESULTS
  Using liquid chromatography mass spectrometry lipidomics techniques for an initial screen of 200 lipid species, significant changes in 79 sphingolipid, glycerophospholipid and cholesterol species were detected in the visual cortex of Parkinson's disease patients (n = 10) compared to controls (n = 10) as assessed by two-sided unpaired t-test (p-value <0.05). False discovery rate analysis confirmed that 73 of these 79 lipid species were significantly changed in the visual cortex (q-value <0.05). By contrast, changes in 17 and 12 lipid species were identified in the Parkinson's disease amygdala and anterior cingulate cortex, respectively, compared to controls; none of which remained significant after false discovery rate analysis. Using gas chromatography mass spectrometry techniques, 6 out of 7 oxysterols analysed from both non-enzymatic and enzymatic pathways were also selectively increased in the Parkinson's disease visual cortex. Many of these changes in visual cortex lipids were correlated with relevant changes in the expression of genes involved in lipid metabolism and an oxidative stress response as determined by quantitative polymerase chain reaction techniques.
  
  
  CONCLUSIONS
  The data indicate that changes in lipid metabolism occur in the Parkinson's disease visual cortex in the absence of obvious pathology. This suggests that normalization of lipid metabolism and/or oxidative stress status in the visual cortex may represent a novel route for treatment of non-motor symptoms, such as visual hallucinations, that are experienced by a majority of Parkinson's disease patients.
authors.affiliation: Neuroscience Research Australia, Sydney, New South Wales, Australia.
authors.forename: Danni
authors.initials: D
authors.lastname: Cheng
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Jenner
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Wei Fun
authors.initials: WF
authors.lastname: Cheong
authors.forename: Todd W
authors.initials: TW
authors.lastname: Mitchell
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Nealon
authors.forename: Woojin S
authors.initials: WS
authors.lastname: Kim
authors.forename: Heather
authors.initials: H
authors.lastname: McCann
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.forename: Brett
authors.initials: B
authors.lastname: Garner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D052439:Lipid Metabolism Disorders / Q000150:complications* / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D014786:Vision Disorders / Q000209:etiology / Q000378:metabolism; D014793:Visual Cortex / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology